目的 探究高糖对大鼠滑膜间充质干细胞（synovial mesenchymal stem cells，SMSCs）衰老的影 响，为SMSCs应用于糖尿病患者骨关节炎的治疗提供风险评估依据。方法 葡萄糖生理浓度（5.5 mmol/L） 作为对照组，高糖（25 mmol/L）作为高糖组，检测大鼠 SMSCs 在高糖刺激下的衰老情况，包括细胞增殖活 性，β⁃半乳糖苷酶（SA⁃β⁃gal）表达，衰老相关表型（SASP）IL6、MMP13、TNFα、CXCL1、IFNβ的mRNA表达，细 胞内线粒体裂解情况，p21 蛋白表达，以及透明质酸的分泌。结果 本实验条件下，高糖刺激不影响大鼠 SMSCs增殖（P = 0.675），SA⁃β⁃gal 染色阳性细胞增加，SMSCs 胞内线粒体裂解增加，线粒体呈碎片化，衰老 相关表型 SASP 的 mRNA 表达增加，MMP13（P = 0.011），TNF、IL⁃6、INFβ（P = 0.000），CXCL1（P = 0.003）， p21 蛋白表达下降（P = 0.00），透明质酸释放降低（P = 0.002）。结论 高糖使大鼠 SMSCs 进入衰老状态， 损害其生物学功能，采用SMCSs 治疗糖尿病患者骨关节炎其临床效果有待商榷。

Objective To investigate the impact of high glucose on senescence of rat synovial mesenchymal stem cells（SMSCs）so as to provide a reference for risk management of SMSCs in the treatment of osteoarthritis in diabetic patients. Methods The rat SMSCs were divided into control group（physiological concentration of glucose with 5.5 mmol/L）and treatment group（high glucose with 25 mmol/L）. The senescence of rat SMSCs was detected， including cell proliferation，SA⁃β⁃Gal staining，mRNA expression of SASP（IL⁃6，MMP⁃13，TNF⁃α，CXCL1，IFN⁃β）， intracellular mitochondrial damage，p21 protein expression，and hyaluronic acid release. Results The high glucose medium did not affect the proliferation of SMSCs in the rats（P = 0.675）. Also，the high glucose medium enhanced the number of SA⁃β⁃Gal staining positive cells，the fragmentation of intracellular mitochondrial，and the mRNA expression of SASP，namely MMP⁃13（P = 0.011），TNF，TL⁃6，INFβ（P = 0.000），CXCL1（P = 0.003）. Meanwhile， the Western blot and ELISA results demonstrated significant down ⁃ regulated expressions of P21（P = 0.00）and hyal⁃ uronic acid（P = 0.002）. Conclusion High glucose induces senescence and biological function impairment of SMSCs in rats. The clinical effect of SMCSs in the treatment of osteoarthritis in diabetic patients remains to be confirmed.